Our studies have demonstrated that diabetes mellitus affects gingival collagen metabolism explaining in part the increased severity of periodontal disease and impaired wound healing associated with this clinically significant systemic factor. More recently, and unexpectedly, we found that diabetes suppressed the loss of collagen, measured as hydroxyproline (hyp), that occurs in inflamed gingiva of systemically-normal (control) rats. Our studies initially implicated diabetes-induced increased collagen crosslinking and decreased leucocyte chemotaxis to explain this defect. Preliminary data now suggests two other important factors: (1) that diabetes may suppress the collagenolytic activity of inflammatory cells, and (2) that the suppressed loss of hyp during inflammation in the diabetic rat may reflect incomplete collagen degradation, and the accumulation of hyp-containing breakdown products in these tissues. Our main proposals are: (a) to assess and characterize the collagenase (and in some experiments, elastase) activity of polymorphonuclear leucocytes (P) and macrophage (M) from control and diabetic humans (P only) and rats (P and M), (b) to assess the effect of diabetes on the in vivo breakdown of collagen, prelabeled with H3-hyp, in uninflamed and inflamed gingiva. H3-hyp loss in these tissues will be assessed at multiple time points to determine the diabetic effect on the rapidly and slowly turning-over pools of collagen. The gingiva will be examined for accumulations of collagen breakdown products, using electrophoretic and chromatographic techniques, since preliminary data suggests their presence in abnormal levels in diabetic tissues, (c) to examine the collagen components in gingiva from control and diabetic humans to determine whether the inflamed diabetic tissues contain collagen breakdown products not seen in the inflamed gingiva of systemically-normal subjects (preliminary data suggests this possibility). Our overall objectives are to use diabetes as a clinically relevant model system to study the role of various altered physiologic processes (eg. altered inflammatory response, collagen metabolism) in the pathogenesis of periodontal breakdown and to clarify how this systemic factor increases the severity of periodontal disease.